Opioid analgesics such as e.g. morphine are the most powerful analgesic drugs. The pain relieving activity of opioid analgesics includes a depressive effect on the central nervous system. The analgesic activity of opioid analgesics such as morphine and deltorphin II can be mediated via different opioid receptors, for example via receptors .mu.-opioid and .delta.-opioid receptors. Opioid analgesics are invaluable for the treatment of severe acute or chronic pain as, for example, may occur in bone degenerative diseases and cancer conditions. They are easy to administer and they provide effective pain relief in most patients. Due to the excellent overall tolerability of opioids the doses of morphine and other strong opioids can be increased to relatively high levels. Yet, in particular upon long term use, there is a development of unacceptable side effects.
These side effects include the development of physical dependence and tolerance, sedation, respiratory depression, hypotension, increase in cerebrospinal fluid pressure, nausea, vomiting and constipation. In some patients, particularly in the chronically ill, the opioid side effects make it impossible to continuously administer sufficiently high dosages to adequately control pain over the needed period of time. There are also some pain conditions that do not sufficiently respond to opioid pain treatment alone. Therefore, there is a constant need for improved opioid containing analgesic combinations with increased analgesic activity which comprise opioid and non-opioid analgesically active agents and which offer the possibility of reducing the opioid dose needed for efficient pain relief and thereby also reducing the opioid side effects that might result from the otherwise required higher dosages.
It is therefore an object of the present invention to provide an opioid containing analgesic composition having high analgesic potency and a reduced propensity for causing undesirable side effects.
It is also an object of the invention to provide a non-opioid substance with analgesic effects showing synergy with the analgesic activity of the opioid, and to provide analgesic compositions comprising an opioid analgesic agent, in particular morphine, and such a synergistically effective non-opioid analgesic agent which allows to reduce the amount of the opioid necessary to achieve effective pain treatment.
It is further an object of the invention to provide a method for producing opioid induced analgesia in larger mammals, in particularly in humans, whereby undesirable side effects of acute and chronic administration of strong opioids are reduced.